The goals of this proposal are two-fold: First, to elucidate the mechanisms involved in inducing a protective immunity to Salmonellosis. The model system will employ the mouse-Salmonella typhimurium interaction. This is to include the parameters of cellular immunity and humoral immunity based on the hypothesis that multiple antigenic stimuli are involved. Antigens will be assessed for (a) their involvement in delayed type hypersensitivity (cellular immunity) by their ability to elicit blastogenesis in lymphocyte cultures of infected or immunized animals. (b) The antibodies induced by such antigens will be assessed for their necessity for protection as determined by passive immunity and correlation of their presence or absence with the protected state, and (c) their ability to induce in mice, either singly or in combination, with and without Freund's adjuvant, a protective state against experimental infection. The second goal involves the development of practical vaccines for humans and animals proceeding from the above findings. In addition, a living attenuated vaccine consisting of streptomycin-dependent mutants will be assessed for (a) the ability to control its in vivo growth by administering the drug to the infected animal, (b) control of its in vivo growth by cultivating it on various concentrations of the antibiotic before inoculation, (c) the requirements for its persistence and/or multiplication in vivo to yield a solid immunity, (d) the safety and practicability of such vaccines will be assessed.